A novel role for macrophage: antigen discrimination of distinct carbohydrate bonds.
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S MacRae
Publications and source records attributed to S MacRae.
Suppression of cytotoxic response to histoincompatible cells. I. Evidence for two types of T lymphocyte-derived suppressors acting at different stages in the induction of a cytotoxic response.
Spleen and thymus cell populations from normal or allograft tolerant mice have been cultured for 5 days with specific alloantigens and examined for their reactivity in three assay systems. No consistent correlation was observed between the production of cytotoxic T cells (CTL) in these cultures and the ability of such cultured cells to inhibit specifically a CML response from fresh normal spleen cells directed to the priming alloantigens. Furthermore, suppressor cells measured in this latter assay were apparently distinct from those able to inhibit the production of cytotoxic lymphocyte precursors (CTLp) from bone marrow stem cells in lethally irradiated bone marrow protected mice. Velocity sedimentation experiments confirmed that both the precursor and effector cells for the two suppressor systems were physically separable, and were distinct from CTLp or CTL, respectively. Precursor cells for the two suppressor systems investigated belong to the short-lived cortical thymus cell population.
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Suppression of cytotoxic response to histoincompatible cells. II. Analysis of the role of two independent T suppressor pools in maintenance of neonatally induced allograft tolerance in mice.
The kinetics of appearance of the precursors of SuppA cells (capable of inhibiting CTLp leads to CTL) or SuppB cells (capable of inhibiting (stem cells leads to CTLp) in neonatal mice, as well as the appearance of SuppA/SuppB cells in mice given neonatal innoculations of semiallogeneic spleen cells has been investigated. The data obtained are consistent with the idea that SuppA cells have a natural role to play in the induction of neonatal tolerance, whereas SuppB cells may be more important for the maintenance of the tolerant state. Unlike the level of SuppB cells, the level of SuppA cells in tolerant mice seems to be modulated by the presence of the tolerizing determinants. Data are provided to show that SuppB cells, once induced in tolerant mice, can adoptively transfer specific allograft unresponsiveness to newborn syngeneic mice in the absence of added tolerizing antigen, whereas SuppA cells are not able to do so. These data fit the notion that SuppB cells may be responsible for the phenotype of clonal deletion.
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Differentiation of functionally active mouse T-lymphocytes from functionally inactive bone marrow precursors.
An investigation has been made of the development of various T cell functions in lethally irradiated mice reconstituted with anti-0 treated spleen or bone marrow cells. Evidence is presented to show that both organs contain a post-thymic precursor pool able to regenerate by 15 days limited T cell responses in thymectomized recipients. A prethymic pool also exists in each organ able to regenerate, at a later date, first a suppressor T cell population and probably later, mature functional T cells involved in helper functions and cell mediated lympholysis. The spleen is apparently a better source of precursors of the suppressor cells than bone marrow, while a poorer source of precursors of the other T cell functions. All T cell functions investigated apparently first appear in large cells which undergo a reversion to small cells without necessarily maturing to their full potential reactivity. By following the kinetics of appearance of T cell functions, and the physical parameters of the cells with which these functions are associated, it is shown that PHA responding and Con A responding cells, cytotoxic T cell progenitors, helper T cells for antibody production and helper T cells for cytotoxicity induction can all at some stage of differentiation be separated from one another.
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Differentiation of functionally active mouse T lymphocytes from functionally inactive bone marrow precursors II. Limited recovery of T-cell responses from mouse bone marrow in tissue culture.
The limited differentiation of mature T cell function from mouse bone marrow in tissue culture is described and compared with similar differentiation occuring in vivo in irradiated bone marrow protected mice. Data are presented to show that a pool of precursors, similar in size to that able to produce early (transient?) regeneration in thymectomized recipients, is responsible for the development of mitogen responsive T cells active in MLC (proliferation) and CML (development of cytotoxic cells) assays. In contrast, a helper cell population which augments antibody formation from T-depleted normal spleen cells derives from a pool of similar precursors yet does not seem to be theta positive. Similarly, larger cells (perhaps typical of those giving rise to suppressor T cells in vivo) give rise to a suppressor cell pool after 4 days of culture, though again only a fraction of this suppressor activity could be attributed to theta positive cells. It is suggested that much of the data for regenration of T lymphocytes in vitro from T-depleted sources needs to be re-interpreted in terms of this evidence for a pool of post-thymic precursors of T cells in such T-deficient cell populations.
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